Can a Man Continue With Resperidol Even With Elevated Prolactin Vevel
Psychiatry (Edgmont). 2004 Nov; 1(3): 29–31.
Published online 2004 Nov.
Hyperprolactinemia Associated with Risperidone
A Case Report and Review of Literature
Ahmed Aboraya, MD, DrPH, 
Jennifer E. Fullen, Pharm D, BCPP, Barbara L. Ponieman, MD, Eugene H. Makela, Pharm D, BCPP, and Melissa Latocha, Pharm D
Abstract
This case report describes a 19-year-old Caucasian woman who presented to a state psychiatric facility with symptoms of depression and auditory hallucinations. She was diagnosed with schizoaffective disorder, depressed type, and was treated with risperidone and sertraline. Soon after initiation of drug therapy, the patient developed galactorrhea and dysmenorrhea, and her prolactin level was 171.6ng/mL (normal level 2.8–29.2ng/mL in adult women). Upon discontinuation of risperidone, the prolactin level dropped to 17.2ng/mL within one week. The patient was treated with quetiapine and titrated up to 800mg daily. Repeated prolactin levels continued to be normal during treatment with quetiapine. This case report and others from literature suggest that risperidone is associated with hyperprolactinemia, and that quetiapine is less likely to be associated with hyperprolactinemia.
Introduction
Prolactin is a hormone produced by the lactotrophs of the anterior pituitary and is composed of a single-chain protein.1 Prolactin plays an important role in the process of reproduction in men and women. It also affects water and electrolyte balance, growth and development, metabolism, immunoregulation, and behavior. Prolactin level is very high in newborn infants and declines during the first few months of life. Among adults, prolactin level is higher in women, especially during pregnancy, and reaches peak level during the night. Thyrotropin-releasing hormone, vasoactive intestinal neuropeptide, opioids, and serotonin [5-hydroxytryptamine (5-HT)] can increase prolactin levels while dopamine can decrease prolactin levels.1,2
Hyperprolactinemia is clinically defined as a plasma prolactin level of >20ng/mL for men and >25ng/mL for women.2 Elevated prolactin in men may cause erectile dysfunction, ejaculatory dysfunction, gynecomastia, and decreased libido. In female subjects, abnormally high prolactin levels may cause menstrual disturbances, galactorrhea, gynecomastia, and sexual dysfunction.2–4 Chronic hyperprolactinemia increases risk for osteoporosis, cardiovascular disease, and breast cancer.2
Antipsychotic medications are used to treat a variety of psychiatric disorders. Conventional neuroleptics, such as haloperidol, fluphenazine, thiothixene, perphenazine, chlorpromazine, and thioridazine have been shown to cause hyperprolactinemia.5–12 The mechanism by which conventional neuroleptics cause increased prolactin is a dopamine blockade in the tubero-infundibular tract of the hypothalamus, which in turn reverses the dopaminergic inhibition of prolactin in the anterior pituitary.13 The length of time it takes for prolactin to increase after initiation of conventional neuroleptics varies from a few hours to nine days.9–11 Neuroleptic-induced hyperprolactinemia is more common in women than men,7 and prolactin increase by conventional neuroleptics is also higher in women.8 The prevalence of sexual dysfunction in patients receiving conventional neuroleptics varies depending on the medication used and can reach 60 percent.14–16
Over the past 15 years, a new class of drugs known as atypical antipsychotics (e.g., clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and ziprasidone) has emerged. These medications offer the advantage of improved efficacy in the treatment of positive and negative symptoms of psychosis, as well as a better side effect profile over the older agents (fewer extra pyramidal side effects and decreased propensity to cause increased prolactin levels).17–23 The decreased tendency of some atypical agents, compared to conventional agents, to produce hyperprolactinemia is related to their weaker and more transient dopamine D2 antagonist effects and their more potent 5-HT2 antagonist effects.24 Although atypical antipsychotic agents, such as olanzapine, quetiapine, and clozapine, have shown to increase prolactin level, this effect is minimal and short-lived. Risperidone, however, is a widely used atypical agent that has shown more pronounced and continuous elevations in prolactin levels due to a stronger, more prolonged dopamine receptor blockade.15–31
This case report demonstrates risperidone was associated with a high prolactin level with resultant adverse effects in a young adult woman, and that changing treatment to quetiapine normalized this prolactin level and reversed the observed side effects.
Case Report
A 19-year-old woman with no significant psychiatric history began to have depressive symptoms that worsened over time. Seven months later, the patient started to experience auditory hallucinations that were sometimes command in nature. No manic or hypomanic symptoms had occurred at any time. The patient was first hospitalized in a psychiatric hospital after a suicide attempt by overdose and was subsequently hospitalized four more times due to similar circumstances. The patient's fourth admission was to William R. Sharpe, Jr. Hospital, a 150-bed, JCAHO-accredited state psychiatric facility, for 82 days. During this admission, the patient was assessed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) by the treating psychiatrist who had full SCAN training.32 Family history was negative for psychiatric illness. The patient had a complete medical work-up, which included a urine drug screen and computerized tomography (CT) of the brain with no significant findings. Magnetic resonance imaging (MRI) of the brain was done with no evidence of hypothalamic or pituitary abnormalities. The patient was diagnosed with schizoaffective disorder, depressed type, and this diagnosis was consistent with previous admissions. The patient had been treated with several different antidepressant and antipsychotic medications, such as fluoxetine and haloperidol.
During this fourth admission to Sharpe Hospital, the patient was treated with sertraline (100mg/day) for depression and levothyroxine (25 micrograms daily) for hypothyroidism. Risperidone was started prior to the fourth admission and was titrated gradually over three weeks from 4mg/day to 10mg/day at the time of admission. The patient complained of dysmenorrhea and galactorrhea. A prolactin level was drawn five days after admission and was 124ng/mL (normal level 2.8–29.2ng/mL in women). Four weeks later, risperidone was decreased to 8mg/day. Three days after the dose of risperidone was reduced, a repeated prolactin measured 171.6ng/mL. Risperidone was stopped due to the high prolactin level and continued galactorrhea and dysmenorrhoea. One week after risperidone was discontinued, the patient was started on quetiapine 100mg/day and titrated to a dose of 400mg/day. Prolactin levels drawn one and two weeks after discontinuation of risperidone and initiation of quetiapine were 17.2ng/mL and 11.4ng/mL, respectively. Quetiapine was increased to 800mg/day and the prolactin level while on this dose was 10.5ng/mL. Two pregnancy tests done during the admission showed negative results. The patient received depot-medroxyprogesterone acetate 150mg IM as a contraceptive measure two weeks prior to discharge.
Discussion
This case demonstrates a clinically significant relationship between risperidone administration and resultant hyperprolactinemia with significant adverse effects. The patient's prolactin level was high when she was treated with risperidone, and the prolactin level dropped by tenfold one week after stopping this medication (from 171.6 to 17.6 ng/mL). The likelihood of risperidone causing hyperprolactinemia is considered probable on the Naranjo scale.33 This rating is based on the following: previous conclusive case reports on this reaction, timing of risperidone administration and hyperprolactinemia, patient's drop of prolactin level upon discontinuation of risperidone, lack of other causes (such as pregnancy) that could have produced hyperprolactinemia, subjective data (dysmenorrhoea and galactorrhea), and objective lab data. Furthermore, the patient's prolactin level remained normal while receiving the maximum dosage of quetiapine (800mg/day).
It is unlikely the co-administration of sertraline in this patient was a factor in causing the increased prolactin level. Risperidone is metabolized to an active metabolite 9-hydroxyrisperidone in the liver via the cytochrome P450 2D6 pathway. While it is known that selective serotonin reuptake inhibitors (SSRIs) can inhibit the 2D6 pathway, the degree to which this occurs varies within the class. Fluoxetine and paroxetine are potent inhibitors of 2D6 and would be most likely to increase plasma levels of risperidone in patients to a clinically measurable degree. Sertraline, citalopram, and escitalopram are weak enzyme inhibitors and would have minor effects on risperidone levels. Coadministration of risperidone with any of these three SSRIs would likely not contribute to clinical changes in a patient. Sertraline and other medications the patient was taking provide no clinically significant drug interactions with risperidone that could lead to increased plasma concentrations.34
This case report is consistent with literature that has shown that risperidone can cause hyperprolactinemia,25–31 while quetiapine is less likely to cause this side effect.17,20,23,35
Conclusion
Risperidone is an atypical antipsychotic that can cause hyperprolactinemia. As new antipsychotic agents enter the market, clinicians need to be aware of hyperprolactinemia as a potential side effect of these medications. Clinicians need to ask patients taking antipsychotic medications about possible sexual side effects and check prolactin levels for those who exhibit symptoms and may be at risk for short and long term side effects of hyperprolactinemia.
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Articles from Psychiatry (Edgmont) are provided here courtesy of Matrix Medical Communications
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010960/
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